We are attempting to use the techniques of gene therapy to understand and treat cardiovascular disease. In particular, we are using adenoviral vectors as a way of efficiently transferring foreign genes into the vessel wall or to the myocardium. Our major focus is to treat vascular restenosis, which occurs in approximately 30-50% of patients after balloon angioplasty. Our hope is to use adenoviral vectors to efficiently and selectively transfer genes, whose products may inhibit smooth muscle cell proliferation at sites of vascular injury. Over the last year, using a replication-deficient recombinant adenovirus encoding a histochemical marker gene (beta-galactosidase) we have demonstrated high efficiency gene transfer to both the myocardium and the vessel wall. Such methods appear 2-3 orders of magnitude more efficient than previous gene transfer strategies. In addition, using a therapeutic adenovirus encoding the thymidine kinase gene of herpes simplex we have shown that adenoviral gene transfer can be used to successfully treat an animal model of vascular restenosis. These initial results suggest that adenoviral-mediated gene transfer may be useful in the treatment of a variety of acquired cardiovascular diseases.